Several techniques have been employed to correct depressed ovoid and linear cutaneous scars. These scars may have been associated with acne vulgaris, varicella, herpes, trauma, surgery, frown lines and wrinkles. Presently available treatments have definite disadvantages. Dermabrasion and chemical peel which involve lowering of the tissue surrounding the scar requires a long convalescence and avoidance of sun for 6 months. Plastic surgery also require long convalescence and is very expensive. Silicone implants have a tendency to migrate, form permanent papules, and peau d'orange and overcorrection frequently occurs. The bovine collagen implant, Zyderm, requires a skin sensitivity test, several treatments and refrigerated storage.
Sheldon K. Gottlieb in U.S. Pat. Nos. 4,006,220 and 4,061,731 describes a new composition which is useful for the repair of depressed cutaneous scars which comprises at least one fibrin stabilizer and plasma. The fibrin stabilizer can be a pulverized absorbable gelatin sponge, aminocaproic acid or derivatives thereof, and preferably a combination of the pulverized and aminocaproic acid. Dr. Gottlieb has also shown in U.S. Pat. Nos. 4,167,945 and 4,191,751 that this composition can also be used to enhance the healing of grafted tissue or to promote the growth of new connective tissue over surface wounds.
The Gottlieb composition is prepared by mixing the absorbable sponge, aminocaproic acid and the patient's plasma to obtain the desired composition which is then introduced into a suitable administration device such as a syringe for administration to the patient. The composition, however, is extremely viscous and difficult to introduce into the syringe. The mixture also has a tendency to separate and dry out. In addition, it is difficult to maintain sterility while storing and mixing the three components.
Since each patient's plasma is unique, it is not possible to provide a physician with a premixed Gottlieb composition. The problem could be resolved by providing a mixture of pulverized gelatin sponge and aminocaproic acid solution to which the physician can add the patient's plasma. Stability of the mixture, however, remains a major disadvantage. Although shelf-life of a product may often be extended by freeze-drying (lyophilization), the nature of the mixture of pulverized gelatin sponge and aminocaproic acid solution mitigates against such a procedure.
A mixture of the absorbable sponge and aminocaproic acid is a sol-gel, i.e., it lies at the phase boundary between a solution and a gel, and is very viscous, heterogeneous and contains a large amount of entrained air. Such a mixture causes a phenomenon during lyophilization known as "bumping". As the vacuum is drawn, the air bubbles in the material being treated are drawn to the surface very quickly and water is drawn off violently carrying solid material with it. This can be minimized by lyophilizing shallow layers of the material spread over a large surface area so that the bumping is randomized and the amount of material lost as a result is, hopefully, statistically insignificant. Such a procedure, however, is quite time consuming and adds significant cost to preparation of the product. Bumping is particularly sever when the surface area is small such as is encountered in a syringe.
It is accordingly the object of this invention to provide a new and economical method of preparing a lyophilized mixture of absorbable powder and aminocaproic acid in administration syringes and also to provide a method for mixing the lyophilized mixture with the patient's plasma. These and other objects of the invention will become apparent to those skilled in this art from the following detailed description.